title: Edaravone protected human brain microvascular endothelial cells from methylglyoxal-induced injury by inhibiting AGEs/RAGE/oxidative stress.
abstract: Subjects with diabetes experience an increased risk of cerebrovascular disease and stroke compared with nondiabetic age-matched individuals. Increased formation of reactive physiological dicarbonyl compound methylglyoxal (MGO) seems to be implicated in the development of diabetic vascular complication due to its protein glycation and oxidative stress effect. Edaravone, a novel radical scavenger, has been reported to display the advantageous effects on ischemic stroke both in animals and clinical trials; however, little is known about whether edaravone has protective effects on diabetic cerebrovascular injury. Using cultured human brain microvascular endothelial cells (HBMEC), protective effects of edaravone on MGO and MGO enhancing oxygen-glucose deprivation (OGD) induced injury were investigated. Cell injury was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) formation, cell account, lactate dehydrogenase (LDH) release and Rhodamine 123 staining. Advanced glycation end-products (AGEs) formation and receptor for advanced glycation end-products (RAGE) expression were measured by western blotting. Cellular oxidative stress was measured by reactive oxygen species (ROS) release. Treatment of MGO for 24 h significantly induced HBMEC injury, which was inhibited by pretreatment of edaravone from 10-100 µmol/l. What's more, treatment of MGO enhanced AGEs accumulation, RAGE expression and ROS release in the cultured HBMEC, which were inhibited by 100 µmol/l edaravone. Finally, treatment of MGO for 24 h and then followed by 3 h OGD insult significantly enhanced cell injury when compared with OGD insult only, which was also protected by 100 µmol/l edaravone. Thus, edaravone protected HBMEC from MGO and MGO enhancing OGD-induced injury by inhibiting AGEs/RAGE/oxidative stress.
authors.affiliation: Department of Pharmacy, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Wenlu
authors.initials: W
authors.lastname: Li
authors.forename: Hongjiao
authors.initials: H
authors.lastname: Xu
authors.forename: Yangmin
authors.initials: Y
authors.lastname: Hu
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Ni
authors.forename: Huimin
authors.initials: H
authors.lastname: Xu
authors.forename: Zhongmiao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Haibin
authors.initials: H
authors.lastname: Dai
mesh_terms: D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply / Q000166:cytology*; D048909:Diabetes Complications / Q000378:metabolism*; D000077553:Edaravone; D042783:Endothelial Cells / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D055806:Microvessels / Q000166:cytology*; D018384:Oxidative Stress / Q000502:physiology*; D011765:Pyruvaldehyde / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D020112:Rhodamine 123; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D013778:Tetrazolium Salts; D013844:Thiazoles; D020112:Rhodamine 123; D011765:Pyruvaldehyde; C022616:thiazolyl blue; D000077553:Edaravone; D000983:Antipyrine